I ANTI-HIV AGENTS. Contents I ANTI-HIV AGENTS II COMPLICATIONS AND SIDE EFFECTS III INFECTIONS IV CANCER. A. Treatments for drug-resistant.

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1 TreatmentUpdate 163 Vol. 19, No. 5 July/August 2007 ISSN Available on the World Wide Web at Contents I ANTI-HIV AGENTS A. Treatments for drug-resistant HIV coming 1 B. Darunavir shows its strength 2 C. Taking PEP to prevent HIV infection results from Denmark 4 II COMPLICATIONS AND SIDE EFFECTS A. Minimizing fat loss comparing nukes 6 B. Bone changes after starting HAART 6 C. Yoga for heart disease 7 D. Abacavir hypersensitivity testing results Montreal 8 III INFECTIONS A. Sex and hepatitis C infection in Germany 9 IV CANCER A. Rise in risk for skin cancer 10 I ANTI-HIV AGENTS A. Treatments for drug-resistant HIV coming In high-income countries, many treatments for HIV are usually available. Despite this bounty of options, once HIV develops the ability to resist one or more treatments, future options become limited. This limitation arises because resistance to one drug in a class of anti-hiv medications often confers a degree of resistance to other members of that class. People with HIV/AIDS (PHAs) may acquire drug-resistant HIV at the time of their infection. Or, in the average treatment-experienced person, over many years HIV gradually acquires the ability to resist the effect of therapy, becoming, in some cases, multi-drug resistant (MDR). This type of highly resistant HIV is difficult to treat. There are several possible ways to try to deal with the problem of drug-resistant HIV. One is to design new drugs that can work against resistant virus. Another is to develop entirely new classes of anti-hiv agents. In high-income countries, PHAs are the beneficiaries of converging research and development programs that have led to new treatment options. Here are some of them: Entry inhibitors These drugs work by blocking a co-receptor called CCR5, which HIV uses to infect cells of the immune system. The entry inhibitor that is currently being released in Canada through an expanded access program is called maraviroc. Integrase inhibitors These drugs work by interfering with an enzyme called integrase, produced by 555 Richmond Street West, Suite 505 Box 1104 Toronto, Ontario M5V 3B1 Canada phone: toll-free: fax: charitable registration number: RR

2 Page 2 TreatmentUpdate 163 Vol. 19 No. 5 which is needed to help HIV take over an infected cell. Two integrase inhibitors are in advanced stages of testing in people: raltegravir and elvitegravir. The integrase inhibitor now being released in Canada through an expanded access program is raltegravir (Isentress, formerly known as MK- 0518). Protease inhibitors (PIs) These drugs work by interfering with the protease enzyme, also needed by HIV-infected cells to produce copies of HIV. Darunavir (Prezista) is designed to be effective against strains of HIV that are resistant to other PIs. Most PIs are taken with a small dose of a boosting agent called ritonavir (Norvir). This drug, also a PI, helps to raise and maintain levels of the PI that needs boosting. Darunavir is a new PI approved for use in Canada. Non-nukes (NNRTIs) These drugs work by impairing the activity of another enzyme needed by HIV called reverse transcriptase. New non-nukes at an advanced stage of testing in people include TMC125 (etravirine) and TMC278 (rilpilvirine). All of these medications may provide some benefit to PHAs who are treatment-experienced. In this and forthcoming issues of TreatmentUpdate, we will present information about these drugs, many of which were discussed at length at the 4th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention that took place from July 22 to 25 in Sydney, Australia as well as other information from the 9th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, that also took place in Australia in July Deeks SG. Protease inhibitors as immunomodulatory drugs for HIV infection. Clinical Pharmacology and Therapeutics 2007 Sep;83(2): B. Darunavir shows its strength Any time a new anti-hiv drug is ready for the final stages of clinical testing, it is usually compared in a clinical trial against an already approved therapy. Although there are many HIV/AIDS treatment guidelines available in Western countries, one of the most comprehensive is developed by the United States federal health ministry, the Department of Health and Human Services (DHHS). At press time, those guidelines suggest that the following protease inhibitors (PIs) are preferred for use in the initial therapy of HIV infection: fosamprenavir/ritonavir (Telzir, Lexiva) lopinavir/ritonavir (Kaletra, Aluvia) atazanavir/ritonavir (Reyataz) These guidelines are regularly revised, so expect changes to this list in the future. Although the DHHS guidelines do offer a choice of PI to use, in practice, for the past several years, lopinavir/r has commonly been used, perhaps because of its strength and long-term effectiveness. As a result, manufacturers of anti- HIV medications who seek to supplant the role of lopinavir/r in treatment conduct clinical trials comparing their medication to that of lopinavir/r. That was recently the case with the PI darunavir (Prezista) in a clinical trial called TITAN. In that study, moderately treatment-experienced PHAs were randomly assigned to receive either darunavir/r or lopinavir/r as part of combination therapy. After one year, more participants taking darunavir had their viral load fall below the 50-copy mark than did those taking lopinavir/r. Researchers in North and South America, Europe, South Africa and Asia screened nearly 800 possible volunteers for TITAN. After narrowing their selection to a pool of 591 participants, researchers randomly assigned PHAs to receive either darunavir/r (298 PHAs) or lopinavir/r (293 PHAs). The average profile of the entire study group at the beginning of the clinical trial was as follows: 21% female, 79% male age 41 years length of HIV infection nine years viral load 20,400 copies CD4+ count 232 cells 33% had symptoms of AIDS in the past 15% were co-infected with hepatitis B or C viruses

3 Treatment history In this study, participants were modestly treatment-experienced, as follows: 52% had used four or more nukes or nucleotide analogues 69% had used at least one protease inhibitor 76% had used at least one non-nuke Tests to assess the level of pre-existing drug resistance were conducted and researchers found that resistance to PIs was generally low. All participants received what the study called an OBR optimized background regimen. This consisted of anti-hiv medications that were judged to be most suitable for each individual participant based on his or her treatment history and the results of resistance testing. Results Effectiveness The study was primarily designed to determine the proportion of participants whose viral load was eventually suppressed below the 400-copy mark (though there were secondary outcomes that are also interesting and will be detailed later). After one year, the results were as follows: darunavir/r 77% lopinavir/r 68% A statistical analysis of this outcome suggests that darunavir/r provides superior virologic suppression to lopinavir/r. This study was designed several years ago. Today, it is expected that new therapies are able to reduce viral load below the 50-copy mark. Using this more stringent assessment, the results were as follows: darunavir/r 71% lopinavir/r 60% This difference was statistically significant. Differences between the two regimens in their ability to suppress viral load occurred as early as six months into the study. Assessing the degree of viral load suppression that each therapy could provide is another way to examine the differences: darunavir/r minus 1.95 logs lopinavir/r minus 1.72 logs TreatmentUpdate 163 Vol. 19 No. 5 Page 3 This difference in viral suppression was statistically significant. Resistance issues The proportion of participants who developed virologic failure was as follows: darunavir/r 10% lopinavir/r 22% In those participants who developed virologic failure, the proportion whose HIV became less susceptible to protease inhibitors or nukes was as follows: darunavir/r 14% lopinavir/r 33% Complications and side effects Overall, commonly reported side effects included the following: diarrhea nausea rash sore throat and sinus infections In the darunavir/r group, the proportion of participants with these side effects was as follows: diarrhea 32% nausea 18% rash 16% sore throat and sinus infection 12% headache 11% In the lopinavir/r group, the proportion of participants with these side effects was as follows: diarrhea 42% nausea 21% sore throat and sinus infection 11% rash 7% Overall, diarrhea was more common among lopinavir/r users and rash was more common in darunavir/r users. Focus on rash Overall, the proportion of rash-related side effects, regardless of severity, was as follows: darunavir/r 16% lopinavir/r 7% Two participants in the darunavir/r group had a severe rash occur. However, one of them was

4 Page 4 TreatmentUpdate 163 Vol. 19 No. 5 taking nevirapine (Viramune), a drug associated with a relatively high risk of rash. In only one of these two cases did the participant need to permanently stop taking darunavir and no one died as a result of the temporary rash. Among people taking lopinavir/r, no one developed a serious rash. Development of AIDS-related infections Four participants in the darunavir/r group and one in the lopinavir/r group developed an AIDSrelated illness as follows: darunavir/r Kaposi s sarcoma (KS) yeast infection of the mouth and throat progressive multifocal leucoencephalopathy (PML) tuberculosis (TB) in the lungs lopinavir/r AIDS-related dementia Deaths A total of five participants died during the study two in the darunavir/r group and three in the lopinavir/r group. The causes of death were as follows: darunavir/r extensive KS tumours in the lungs leading to lung failure blood poisoning from a bacterial infection of the lungs lopinavir/r sudden heart failure complicated by pneumonia sudden heart failure the cause of death in the third person taking lopinavir/r was not known at the time of the study analysis Lipids Levels of lipids cholesterol and triglycerides often increase in PHAs who take HAART, particularly combinations involving even a small dose of ritonavir. The proportion of participants in each group with moderate or highly elevated levels of lipids was as follows: darunavir/r increased total cholesterol: 32% increased LDL-c (so-called bad cholesterol): 19% increased triglycerides: 19% lopinavir/r increased total cholesterol: 29% increased LDL-c :17% increased triglycerides: 25% Formulation issues The formulation of lopinavir/r used in this study was generally the older capsule formulation. A more stable formulation that is resistant to heat, Kaletra tablets, is in widespread use in many highincome countries. It is possible that had this formulation been available and in widespread use during the study fewer differences might have emerged between darunavir/r and lopinavir/r. However, until there is a trial using the new formulation, any theories about what might have happened are speculation. Summary Overall, this study found that combination therapy with either darunavir/r or lopinavir/r was effective in the treatment of moderately treatmentexperienced PHAs. Both combinations were able to suppress viral load below the 400-copy mark. Darunavir/r appeared to be more effective than lopinavir/r at suppressing viral load below the 50-copy mark. Despite this difference, about half of the participants in each group had their CD4+ cell counts climb above the 350-cell mark. Darunavir/r was associated with an increased risk of rash, while lopinavir/r was associated with an increased risk of diarrhea. Both combinations have the potential to be an effective part of combination HIV therapy. REFERENCES: 1. Valdez-Madruga J, Burger DS, McMurchie M, et al. Comparison of 48-week efficacy and safety of darunavir/ritonavir (DRV/r) with lopinavir/ritonavir (LPV/r) in LPV/r-naïve, treatment-experienced patients: a randomised, controlled phase III trial (TITAN). Program and abstracts of the 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 2007, Sydney, Australia. Abstract TUAB European Medicines Agency (EMEA). Committee for Proprietary Medicinal Products. Points to consider on switching between superiority and non-inferiority. 27 July C. Taking PEP to prevent HIV infection results from Denmark Taking highly active antiretroviral therapy (HAART) soon after accidental exposure to HIV may help prevent this virus from infecting and spreading throughout the body. Using HAART

5 TreatmentUpdate 163 Vol. 19 No. 5 Page 5 to prevent infection is called PEP post-exposure prophylaxis. In Denmark, researchers have been collecting information on the use of PEP (such as who used it and why) and its outcomes between 1998 and In Denmark, PEP can only be provided by specialists working in infectious disease clinics. Before 2004, the recommended regimen for PEP was as follows: indinavir (Crixivan) AZT (zidovudine, Retrovir) 3TC (lamivudine, Epivir) In 2004, the PEP regimen was changed to this: lopinavir/ritonavir (Kaletra) AZT 3TC PEP is meant to be taken for 28 days or four weeks. For their report, researchers analysed their database of information collected from surveys and laboratory test results on 632 people. Results A total of 374 people received PEP after a potential sexual exposure to HIV. Here is their basic profile: 22% female, 78% male 57% of the men were bisexual or gay PEP was started about 11 hours after potential exposure to HIV, on average A total of 258 people received PEP following exposure to potentially infectious fluids through injuries because of needle-sticks, cuts or spills. Here is their basic profile: 65% female, 35% male these people were largely health care workers PEP was started an average of two hours after exposure Over time, exposure to HIV in a health care setting ranged from between 20 and 40 cases each year. But with sexual exposure, the number of cases rose steadily year after year, with more than 80 cases occurring in In the case of sexual exposure, unprotected anal sex (either insertive or receptive intercourse) accounted for nearly 60% of exposures. In a small number of these cases (23 people), PEP was prescribed more than once. And in 2006, nine people who had received PEP in the past did so again. Six of these nine were gay or bisexual men. In one of these nine men, HIV exposure led to infection. The research team noted that this man had repeated bouts of unsafe sex before, during and after his use of PEP, which may have accounted for the failure of his regimen. This last point also highlights that there are limits to the effectiveness of PEP. Staying on a regimen The use of HIV medications usually involves taking several pills once or twice daily. For people who are not used to this, such regimens can be difficult. HAART also has short-term side effects that can include headache, nausea, vomiting and diarrhea. Here is the breakdown of the proportion of PEP users who were able to complete their regimens: sexual exposure to HIV: 62% completed their regimen occupational exposure to HIV: 46% completed their regimen The most common reason for discontinuing PEP prematurely was that doctors found out that the potential source of exposure was HIV negative. Another reason was the tolerability of HIV medications. Overall, the Danish report suggests the following: PEP is easily available in Denmark. Repeated use of PEP by the same person is uncommon. It is difficult to assess the effectiveness of PEP based on the type of study design used by the Danish researchers. However, very few cases of HIV infection following exposure and PEP seem to have occurred. The Danish team notes that PEP can only be prescribed by a small number of infectious disease clinics with HIV treatment experience. This ensures a qualified risk assessment [following potential exposure] and a uniform and rational use of PEP.

6 Page 6 TreatmentUpdate 163 Vol. 19 No Lunding S, Katzenstein TL, Kronborg G, et al. Danish post-exposure prophylaxis (PEP) registry: 10 years experience with the use of PEP following HIV exposure. Program and abstracts of the 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 2007, Sydney, Australia. Poster MOPDC03. II COMPLICATIONS AND SIDE EFFECTS A. Minimizing fat loss comparing nukes The loss of the fatty layer under the skin (subcutaneous fat) is known as lipoatrophy. This side effect is generally associated with the use of certain nukes, particularly the following: d4t stavudine (Zerit) AZT zidovudine (Retrovir) Researchers in the United States studied three different combinations of nukes in PHAs who were starting their first regimen of HAART. The purpose of this study was to monitor long-term changes in subcutaneous fat among participants. The study team found that fat loss did not occur with the following combination of nukes: abacavir ABC (Ziagen) 3TC lamivudine (Epivir) Researchers enrolled 308 participants with the following average profile at the start of the study: 20% female, 80% male age 38 years CD4+ count 208 cells HIV viral load 100,000 copies 35% of participants had previously experienced an AIDS-related illness 62% were tobacco smokers 22% had hepatitis C virus (HCV) infection 7% had hepatitis B virus (HBV) infection An unfortunate aspect of this study is that participants were not given one of the three nuke combinations in a random fashion. Randomization helps to reduce bias when interpreting the results of a study. Participants were divided into three groups based on the combination of nukes that was part of their regimen: d4t + 3TC 63 participants AZT + 3TC 192 participants ABC + 3TC 53 participants Changes in body fat were assessed by skin-fold measurements in the arms, thighs and abdomen. Although not as precise as the use of low-dose X- ray scans called DEXA, skin-fold measurements have been used for many years to assess body composition and are much cheaper than DEXA scans. On average, participants remained in the study for between two and three years. Results Initially, all participants gained weight, particularly fat in their limbs. However, after about the first year of therapy this changed. Specifically, participants who received regimens containing d4t or AZT experienced a similar degree of subcutaneous fat loss. However, those PHAs taking abacavir and 3TC were likely to gain a small amount of fat in their legs and arms. Different tissues behave differently An interesting aspect of this study was the finding that different parts of the body lost fat at different rates. For instance, fat loss in the upper trunk was slower than fat loss in the lower trunk. Why this happened is not yet clear. The findings from this study confirm those from other studies in which d4t use (and, to a lesser extent, AZT) is associated with the loss of the fatty layer under the skin. Shlay JC, Sharma S, Bartsch G, et al. Long-term subcutaneous tissue changes among antiretroviral naïve persons initiating three nucleoside regimens. Programs and abstracts of the 9th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, July 2007, Sydney, Australia. Abstract P-17. B. Bone changes after starting HAART Thinning bones appear to be common in some PHAs in high-income countries. The reasons for the loss of bone density are complex and may be related to a combination of factors, including long-term HIV infection. For more details about

7 TreatmentUpdate 163 Vol. 19 No. 5 Page 7 bone health, please see TreatmentUpdate 162, available at: Researchers in Toulouse, France, undertook a study to assess changes in the bones of PHAs after they began taking HAART. Their findings suggest that the bones of some PHAs may continue to get thinner after the initiation of HAART. Researchers randomly assigned participants to one of the following regimens: two nukes + a protease inhibitor (PI) 36 PHAs two nukes + a non-nuke 36 PHAs At regular intervals, extensive analysis of blood samples was done. One analysis during the study assessed levels of enzymes and compounds associated with bone formation (such as bone alkaline phosphate and osteocalcin) and the breakdown of bone (such as beta cross laps). These latter substances are amino acids produced from the breakdown of connective tissue. Bone density was measured using low-dose X-ray scans called DEXA. The average profile of participants at the start of the study was as follows: age 39 years weight 68 kg/150 lbs body mass index 23 (Body mass index, or BMI, is the result of dividing a person s weight in kilograms by the square of their height in metres. This helps to give physicians a sense of how fat or thin patients are.) CD4+ count 245 cells viral load 79,000 copies Commonly used nuke combinations in this study were as follows: AZT + 3TC tenofovir (Viread) + 3TC tenofovir + FTC (emtricitabine) ABC + 3TC Results At the time results were presented, 24 participants taking protease inhibitors and 25 taking non-nukes had been in the study for nine months. Other participants are at an earlier stage of the study. In both groups, weight and BMI increased over the course of the study. Based on lab tests, bone formation and bone breakdown increased in both groups. However, using DEXA scans, bone density of the spine decreased slightly in the PI group compared to the non-nuke group. Among participants in the non-nuke group, bone density appeared to remain stable. Overall, this study suggests that some PHAs may develop a slight decrease in bone density after starting HAART. But here are some points to bear in mind when trying to assess the results: The number of participants in this study was relatively small and its conclusions can only be considered preliminary. A longer period of monitoring may be needed to get a more accurate sense of changes in bone density. Researchers did not apparently take into account common risk factors for bone loss, such as tobacco use or a history of exposure to corticosteroids, when they analysed the results. These risk factors could have had an effect on their results. The study is continuing and more results are expected after two years. Bonnet E, Mabile L, Ruidavets JB, et al. Important changes in bone metabolism soon after commencing HAART. Programs and abstracts of the 9th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, July 2007, Sydney, Australia. Abstract C. Yoga for heart disease As HAART users age, their risk for cardiovascular disease increases. Although many medications are available to lower cholesterol levels and blood pressure, potential therapies that do not involve medications to achieve a similar effect are understudied. Because yoga is generally safe and may help reduce stress and anxiety, it is possible that this form of therapy could help reduce blood pressure. Some researchers in the United States have been interested in a particular form of yoga called Ashtanga yoga because it is much more strenuous

8 Page 8 TreatmentUpdate 163 Vol. 19 No. 5 than other forms of yoga. Engaging in Ashtanga yoga will likely cause people to burn more calories and strengthen muscles, perhaps faster than other forms of yoga. To find out if Ashtanga yoga might benefit PHAs, American researchers conducted a short study, finding several beneficial results. The study team enrolled 41 PHAs (25% women, 75% men), all of whom were taking HAART and who had at least one risk factor for cardiovascular disease. They had the following average profile: length of time HIV positive 11 years weight 73 kg/161 lbs CD4+ count 507 cells 89% of participants had a viral load below the 50-copy mark All participants received monthly nutritional counseling from a research dietitian. PHAs were randomly assigned to one of the following groups: yoga five months of individual and group instruction for Ashtanga yoga from a certified instructor. Yoga was practiced two to three times weekly. standard of care besides HAART, no additional therapy During the study, blood samples were regularly collected and assessments of body composition and blood pressure were performed. Results Only a portion of enrollees had completed the study at the time of preliminary data analysis, as follows: yoga 17 participants standard of care 10 participants Among the standard of care group there were no significant changes in any of the factors measured. However, among the yoga group, researchers found a small but statistically significant reduction in the following: total cholesterol triglycerides blood pressure No significant changes in CD4+ counts, viral load or blood sugar were detected between the two groups over the course of the study. Analysis of the participants diets suggested that they were similar. In summary, the preliminary analysis of the study suggests that a simple and relatively inexpensive intervention Ashtanga yoga is safe and associated with modest improvement in some factors that affect the risk for cardiovascular disease in PHAs. Mondy K, Cade WT, Reeds DN, et al. Ashtanga yoga intervention modestly improves cardiovascular disease risk parameters in dyslipidaemic HIV+ subjects with central adiposity. Programs and abstracts of the 9th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, July 2007, Sydney, Australia. Poster P-51. D. Abacavir hypersensitivity testing results Montreal The nuke abacavir (ABC, Ziagen) is also found in the following medications, co-formulated in one pill: Kivexa ABC + 3TC Trizivir ABC + 3TC + AZT Abacavir is a potent and generally safe HIV medication. Importantly, ABC is not linked to changes in body shape as is d4t and, to a lesser extent, AZT. However, in up to about 8% of PHAs given abacavir, a hypersensitivity reaction can occur. For more information about this, please see our Fact Sheet available at: The good news is that a blood test called HLA testing is increasingly available at major infectious disease clinics in large urban centres across Canada. This blood test checks for the presence of genetic material called HLA-B*5701, which is associated with a high risk of developing this reaction. PHAs who test positive for this genetic material should not use abacavir. Researchers at Montreal s Clinique l Actuel, a large community clinic caring for several thousand PHAs, recently reviewed their records to find out why some PHAs stopped using abacavir.

9 TreatmentUpdate 163 Vol. 19 No. 5 Page 9 Their review focused on 1,052 of the clinic s patients (8% female, 92% male), all of whom had, at some point, used abacavir. Their basic profile was as follows: average age 46 years length of time diagnosed with HIV 12 years In general, the research team found that 311 PHAs stopped using abacavir. Of these, 71% did so because their doctors suspected that they might have been undergoing a hypersensitivity reaction. This judgment was made in the time before abacavir hypersensitivity testing was available. By later analyzing blood samples and testing them for the presence of HLA-B*5701, researchers found that these same 71% of PHAs did not have this genetic marker and very likely did not experience a hypersensitivity reaction to abacavir. Testing for the genetic marker before starting abacavir therapy will greatly reduce the potential worry faced by PHAs and their doctors about the risk of a hypersensitivity reaction to this drug. Trottier B, Thomas R, Nguyen VK, et al. How effective HLA screening can reduce the early discontinuation of abacavir in real life. Program and abstracts of the 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 2007, Sydney, Australia. Abstract MOPEB002. III INFECTIONS A. Sex and hepatitis C infection in Germany Since at least 2001, clinics in Western Europe have been reporting that some HIV positive men who were not infected with hepatitis C virus (HCV) have subsequently become co-infected with HCV. Most of these men did not engage in the injection of street drugs. To find out how these infections might have happened, researchers in Berlin and Bonn, Germany, collaborated on a large study. Between September 2006 and January 2007, researchers recruited 22 HIV positive men who had recently become co-infected with HCV. These men were interviewed and compared with another group of 44 HIV positive men of similar age and lifestyle who did not have HCV. This second group was called the control group. Most men in the study were between the ages of 30 and 44 years. They were extensively surveyed about their habits involving sex and substance use. Results Although this study had a relatively small number of participants, the research team arrived at the following conclusions: The transmission of HCV among men who have protected anal intercourse with men seems to take place in the context of several intersecting practices. Among study participants, group sex was common, particularly among men who became co-infected with HCV. (Having sex with many partners increases the risk of exposure to germs, including HCV). Rectal bleeding was more common during sex among men who became co-infected with HCV. This may have occurred because of the use of large objects toys and forearms. Sharing sex toys could lead to infection with HCV and other germs. The risk of rectal injuries increased when participants used sildenafil (Viagra) and related medications, because this can prolong intercourse by the insertive partner. The researchers noted that many men who became co-infected with HCV reported the use of so-called party drugs. Exposure to these drugs, including cocaine and crystal meth, could help dry out the normally damp tissues lining the nose and anus. In turn, this could lead to bleeding when engaging in substance use or sex. Moreover, cocaine, crystal meth and other such drugs may give users a feeling of invulnerability, impairing thinking and judgment. This could cause them to be less concerned about protection from infection. There is also the possibility that street drugs could weaken the immune system and its defenses against HCV and other germs. This possibility is being studied.

10 Page 10 TreatmentUpdate 163 Vol. 19 No. 5 Another possible risk factor is surgery; participants who were co-infected were more likely to report exposure to recent surgery possibly removal of anal warts, circumcision or repairs of rectal punctures. However, more research needs to be done to assess the relation, if any, between surgery and HCV infection in these particular cases. The German researchers noted that a complex interaction between sexual practices and the use of street drugs is apparently associated with HCV transmission. They add that HIV prevention messages need to be strengthened, going beyond warnings about unprotected anal sex. These could include at least the following: The use of street or party drugs increases the risk of transmitting many germs, including HIV and HCV. This can happen because these drugs can dry mucosal tissues, such as those in the nose and anus, leading to bleeding and infection. These substances also impair thinking and judgment factors which can cause users to be less protective about their health and the health of their partner(s). Condoms are an important part of protecting yourself and your partners from HCV and other germs. However, other steps are needed, such as learning to disinfect sex toys before use and not sharing them. Avoiding the contamination of lubricant may also be an important step. Researchers found that the use of condoms during anal intercourse may not be enough to provide protection from HCV. Based on their findings, additional measures are suggested. Clearly, these findings are just the first step and more interviews with recently infected PHAs need to be done to confirm these details, perhaps in other countries. Bear in mind that because this study is partially based on people s reports about their sexual and substance-using behaviour, it may not be completely accurate. Schmidt AJ, Vogel M, Rockstroh JK, et al. Risk factors for hepatitis C in HIV positive MSM. A preliminary evaluation of a case control study. Program and abstracts of the 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 2007, Sydney, Australia. Abstract MOPEB037. IV CANCER A. Rise in risk for skin cancer reported People who have weakened immune systems, such as those who have transplanted organs or HIV infection, are at increased risk for cancer, including skin cancer. At the beginning of the AIDS epidemic in North America, reports of one cancer affecting the skin (and later, other organs) became increasingly common. This cancer is called Kaposi s sarcoma (KS). In 1996, when HAART became available in high-income countries, KS often regressed or went into remission as PHAs immune systems strengthened. However, HAART cannot completely restore the immune system, even with prolonged use. And as PHAs age, their immune systems slowly degrade. Some researchers have noticed that PHAs may be at risk for other forms of cancer affecting the skin. To confirm these findings, researchers in San Diego conducted a study. Researchers reviewed information collected in a database from 4,566 PHAs between the years 1987 and The study team focused on the following cancers: KS malignant melanoma (MM) basal cell carcinoma (BCC) squamous cell carcinoma (SCC) Results Researchers found that during the study period nearly 6% of PHAs developed a form of skin cancer. Nine PHAs developed more than one type of skin cancer as follows: Three PHAs developed KS after they had been diagnosed with another form of skin cancer. Four PHAs developed MM and two other PHAs developed SCC after first being diagnosed with a different skin cancer. The good news is that most of the cancers (83%) occurred in the time before HAART was available and, in these cases, it was usually KS. After HAART became available, cases of skin cancer were usually diagnosed as BCC, SCC or MM.

11 TreatmentUpdate 163 Vol. 19 No. 5 Page 11 Compared to the average HIV negative person in the United States, PHAs in this study were twice as likely to get BCC. Also, PHAs had a risk for MM that was three times greater. However, the risk of SCC was not statistically different from that of HIV negative people. In general, PHAs with these types of skin cancer were likely to have this profile: 42 years old male white have had an AIDS-related illness Due to these findings, the study team suggested that doctors consider screening some PHAs for skin cancer. Crum-Cianflone N, Marconi V, Weintrob A, et al. Increased incidence of skin cancers among HIV-infected persons. Program and abstracts of the 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 2007, Sydney, Australia. Abstract MOPEB086.

12 Page 12 TreatmentUpdate 163 Vol. 19 No. 5 Disclaimer Decisions about particular medical treatments should always be made in consultation with a qualified medical practitioner knowledgeable about HIV-related illness and the treatments in question. The Canadian AIDS Treatment Information Exchange (CATIE) in good faith provides information resources to help people living with HIV/AIDS who wish to manage their own health care in partnership with their care providers. Information accessed through or published or provided by CATIE, however, is not to be considered medical advice. We do not recommend or advocate particular treatments and we urge users to consult as broad a range of sources as possible. We strongly urge users to consult with a qualified medical practitioner prior to undertaking any decision, use or action of a medical nature. We do not guarantee the accuracy or completeness of any information accessed through or published or provided by CATIE. Users relying on this information do so entirely at their own risk. Neither CATIE nor the Public Health Agency of Canada nor any of their employees, directors, officers or volunteers may be held liable for damages of any kind that may result from the use or misuse of any such information. The views expressed herein or in any article or publication accessed or published or provided by CATIE are solely those of the authors and do not reflect the policies or opinions of CATIE or the views of the Public Health Agency of Canada. Permission to Reproduce This document is copyrighted. It may be reprinted and distributed in its entirety for non-commercial purposes without prior permission, but permission must be obtained to edit its content. The following credit must appear on any reprint: This information was provided by the Canadian AIDS Treatment Information Exchange (CATIE). For more information, contact CATIE at Writer Editor Credits Sean Hosein RonniLyn Pustil CATIE, Vol. 19, No. 5 July/August 2007 Production of this newsletter has been made possible through a financial contribution from the Public Health Agency of Canada. What CATIE Does The Canadian AIDS Treatment Information Exchange (CATIE) is committed to improving the health and quality of life of all people living with HIV/AIDS in Canada. CATIE serves people living with HIV/AIDS, and the people and organizations that support them, by providing accessible, accurate, unbiased and timely treatment information. CATIE provides such information through a comprehensive Web site, a bilingual toll-free phone service, electronic and print publications, a national reference library and workshops and exhibits at conferences across Canada. CATIE Publications TreatmentUpdate CATIE s flagship treatment digest on cutting-edge developments in HIV/AIDS research and treatment. Subscribe to TreatmentUpdate and automatically receive an notifying you the moment a new issue is available on-line or contact us at to receive a print subscription. A Practical Guide to HAART The latest on what is known about the various aspects of treatment, including a description of the virus and the immune system, the stages of HIV disease, the tests used to assess health status, and anti-hiv medications. A Practical Guide to HIV Drug Side Effects The latest on what is known about various side effects related to treatment, from appetite loss to sexual difficulties, and tips for countering or preventing them. The Practical Guide series also includes: A Practical Guide to Nutrition A Practical Guide to Complementary Therapies A Practical Guide to Herbal Therapies The Positive Side magazine Holistic health information and views for PHAs. Fact Sheets & Supplement Sheets Concise overviews of conditions, symptoms, medications, side effects, complementary therapies, vitamins, herbs and other treatment issues. pre*fix A harm reduction booklet for HIV+ drug users. Contact CATIE by info@catie.ca on the Web: by telephone: (toll-free) by fax: by post: Richmond Street W Box 1104 Toronto, Ontario M5V 3B1 Canada